Sant Snehal, Wang Dan, Abidi Minhal, Walker Gwyneth, Ferrell Nicholas
Department of Medicine, Division of Nephrology, Vanderbilt University Medical Center, United States.
Department of Medicine, Division of Nephrology, Vanderbilt University Medical Center, United States; Department of Biomedical Engineering, Vanderbilt University, United States; Vanderbilt Center for Kidney Disease, United States.
J Mech Behav Biomed Mater. 2021 Feb;114:104220. doi: 10.1016/j.jmbbm.2020.104220. Epub 2020 Nov 22.
Decellularized organs have the potential to be used as scaffolds for tissue engineering organ replacements. The mechanical properties of the extracellular matrix (ECM) following decellularization are critical for structural integrity and for regulation of cell function upon recellularization. Advanced glycation end products (AGEs) accumulate in the ECM with age and their formation is accelerated by several pathological conditions including diabetes. Some AGEs span multiple amino acids to form crosslinks that may alter the mechanical properties of the ECM. The goal of this work was to evaluate how sugar-induced modifications to the ECM affect the mechanical behavior of decellularized kidney. The compressive and tensile properties of the kidney ECM were evaluated using an accelerated model of AGE formation by ribose. Results show that ribose modifications significantly alter the mechanical behavior of decellularized kidney. Increased resistance to deformation corresponds to increased ECM crosslinking, and mechanical changes can be partially mitigated by AGE inhibition. The degree of post-translational modification of the ECM is dependent on the age and health of the organ donor and may play a role in regulating the mechanical properties of decellularized organs.
去细胞化器官有潜力用作组织工程器官替代物的支架。去细胞化后细胞外基质（ECM）的力学性能对于结构完整性以及再细胞化时细胞功能的调节至关重要。随着年龄增长，晚期糖基化终末产物（AGEs）在ECM中积累，并且在包括糖尿病在内的几种病理状况下其形成会加速。一些AGEs跨越多个氨基酸形成交联，这可能会改变ECM的力学性能。这项工作的目标是评估糖对ECM的修饰如何影响去细胞化肾脏的力学行为。通过核糖使用AGE形成的加速模型评估肾脏ECM的压缩和拉伸性能。结果表明，核糖修饰显著改变了去细胞化肾脏的力学行为。对变形的抵抗力增加对应于ECM交联增加，并且通过抑制AGE可部分减轻力学变化。ECM的翻译后修饰程度取决于器官供体的年龄和健康状况，并且可能在调节去细胞化器官的力学性能中起作用。
